Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Intramolecular interactions mediate pH regulation of connexin43 channels.
Morley GE
,
Taffet SM
,
Delmar M
.
???displayArticle.abstract???
We have previously proposed that acidification-induced regulation of the cardiac gap junction protein connexin43 (Cx43) may be modeled as a particle-receptor interaction between two separate domains of Cx43: the carboxyl terminal (acting as a particle), and a region including histidine 95 (acting as a receptor). Accordingly, intracellular acidification would lead to particle-receptor binding, thus closing the channel. A premise of the model is that the particle can bind its receptor, even if the particle is not covalently bound to the rest of the protein. The latter hypothesis was tested in antisense-injected Xenopus oocyte pairs coexpressing mRNA for a pH-insensitive Cx43 mutant truncated at amino acid 257 (i.e., M257) and mRNA coding for the carboxyl terminal region (residues 259-382). Intracellular pH (pHo) was recorded using the dextran form of the proton-sensitive dye seminaphthorhodafluor (SNARF). Junctional conductance (Gj) was measured with the dual voltage clamp technique. Wild-type Cx43 channels showed their characteristic pH sensitivity. M257 channels were not pH sensitive (pHo tested: 7.2 to 6.4). However, pH sensitivity was restored when the pH-insensitive channel (M257) was coexpressed with mRNA coding for the carboxyl terminal. Furthermore, coexpression of the carboxyl terminal of Cx43 enhanced the pH sensitivity of an otherwise less pH-sensitive connexin (Cx32). These data are consistent with a model of intramolecular interactions in which the carboxyl terminal acts as an independent domain that, under the appropriate conditions, binds to a separate region of the protein and closes the channel. These interactions may be direct (as in the ball-and-chain mechanism of voltage-dependent gating of potassium channels) or mediated through an intermediary molecule. The data further suggest that the region of Cx43 that acts as a receptor for the particle is conserved among connexins. A similar molecular mechanism may mediate chemical regulation of other channel proteins.
Arellano,
Calmodulin acts as an intermediary for the effects of calcium on gap junctions from crayfish lateral axons.
1988, Pubmed
Arellano,
Calmodulin acts as an intermediary for the effects of calcium on gap junctions from crayfish lateral axons.
1988,
Pubmed
Armstrong,
Inactivation of the sodium channel. II. Gating current experiments.
1977,
Pubmed
Barrio,
Gap junctions formed by connexins 26 and 32 alone and in combination are differently affected by applied voltage.
1991,
Pubmed
,
Xenbase
Bennett,
Gap junctions: new tools, new answers, new questions.
1991,
Pubmed
Bennett,
Biophysics of gap junctions.
1992,
Pubmed
Beyer,
Connexin43: a protein from rat heart homologous to a gap junction protein from liver.
1987,
Pubmed
Blank,
Cytosolic pH measurements in single cardiac myocytes using carboxy-seminaphthorhodafluor-1.
1992,
Pubmed
Britz-Cunningham,
Mutations of the Connexin43 gap-junction gene in patients with heart malformations and defects of laterality.
1995,
Pubmed
Bruzzone,
Expression of chimeric connexins reveals new properties of the formation and gating behavior of gap junction channels.
1994,
Pubmed
,
Xenbase
Delmar,
Effects of increasing intercellular resistance on transverse and longitudinal propagation in sheep epicardial muscle.
1987,
Pubmed
Delmar,
Effects of changes in excitability and intercellular coupling on synchronization in the rabbit sino-atrial node.
1986,
Pubmed
Dumont,
Oogenesis in Xenopus laevis (Daudin). I. Stages of oocyte development in laboratory maintained animals.
1972,
Pubmed
,
Xenbase
Dunham,
Immunolocalization and expression of functional and nonfunctional cell-to-cell channels from wild-type and mutant rat heart connexin43 cDNA.
1992,
Pubmed
,
Xenbase
Ek,
Role of histidine 95 on pH gating of the cardiac gap junction protein connexin43.
1994,
Pubmed
,
Xenbase
Esinduy,
In vitro growth inhibition of neoplastically transformed cells by non-transformed cells: requirement for gap junctional intercellular communication.
1995,
Pubmed
Fishman,
Functional analysis of human cardiac gap junction channel mutants.
1991,
Pubmed
Granot,
Phosphorylation and expression of connexin-43 ovarian gap junction protein are regulated by luteinizing hormone.
1994,
Pubmed
Hoshi,
Biophysical and molecular mechanisms of Shaker potassium channel inactivation.
1990,
Pubmed
,
Xenbase
Koval,
Transfected connexin45 alters gap junction permeability in cells expressing endogenous connexin43.
1995,
Pubmed
Kramer,
Potassium channel inactivation peptide blocks cyclic nucleotide-gated channels by binding to the conserved pore domain.
1994,
Pubmed
,
Xenbase
Lang,
Molecular cloning of a rat uterine gap junction protein and analysis of gene expression during gestation.
1991,
Pubmed
Lazrak,
Gap junction gating sensitivity to physiological internal calcium regardless of pH in Novikoff hepatoma cells.
1993,
Pubmed
Liu,
A structural basis for the unequal sensitivity of the major cardiac and liver gap junctions to intracellular acidification: the carboxyl tail length.
1993,
Pubmed
,
Xenbase
Loo,
pp60src-mediated phosphorylation of connexin 43, a gap junction protein.
1995,
Pubmed
Moreno,
Human connexin43 gap junction channels. Regulation of unitary conductances by phosphorylation.
1994,
Pubmed
Noma,
Dependence of junctional conductance on proton, calcium and magnesium ions in cardiac paired cells of guinea-pig.
1987,
Pubmed
Reaume,
Cardiac malformation in neonatal mice lacking connexin43.
1995,
Pubmed
Risek,
Modulation of gap junction transcript and protein expression during pregnancy in the rat.
1990,
Pubmed
Saffitz,
The molecular basis of anisotropy: role of gap junctions.
1995,
Pubmed
Spray,
Physiology and pharmacology of gap junctions.
1985,
Pubmed
Spray,
Equilibrium properties of a voltage-dependent junctional conductance.
1981,
Pubmed
,
Xenbase
Spray,
Structure-activity relations of the cardiac gap junction channel.
1990,
Pubmed
Spray,
Electrophysiological properties of gap junctions between dissociated pairs of rat hepatocytes.
1986,
Pubmed
Stauffer,
Structure of gap junction channels.
1992,
Pubmed
Stauffer,
The gap junction proteins beta 1-connexin (connexin-32) and beta 2-connexin (connexin-26) can form heteromeric hemichannels.
1995,
Pubmed
Suchyna,
Identification of a proline residue as a transduction element involved in voltage gating of gap junctions.
1993,
Pubmed
,
Xenbase
Tabb,
An immunochemical and immunocytologic study of the increase in myometrial gap junctions (and connexin 43) in rats and humans during pregnancy.
1992,
Pubmed
Takahashi,
Rat brain serotonin receptors in Xenopus oocytes are coupled by intracellular calcium to endogenous channels.
1987,
Pubmed
,
Xenbase
Toro,
Structural determinants in the interaction of Shaker inactivating peptide and a Ca(2+)-activated K+ channel.
1994,
Pubmed
Unwin,
Structure of the junction between communicating cells.
1980,
Pubmed
Unwin,
Acetylcholine receptor channel imaged in the open state.
1995,
Pubmed
Unwin,
Two configurations of a channel-forming membrane protein.
,
Pubmed
Werner,
Gating properties of connexin32 cell-cell channels and their mutants expressed in Xenopus oocytes.
1991,
Pubmed
,
Xenbase
White,
Selective interactions among the multiple connexin proteins expressed in the vertebrate lens: the second extracellular domain is a determinant of compatibility between connexins.
1994,
Pubmed
,
Xenbase
White,
Functional analysis of selective interactions among rodent connexins.
1995,
Pubmed
,
Xenbase
Yamamoto,
On the organization of astrocytic gap junctions in rat brain as suggested by LM and EM immunohistochemistry of connexin43 expression.
1990,
Pubmed
Zagotta,
Restoration of inactivation in mutants of Shaker potassium channels by a peptide derived from ShB.
1990,
Pubmed
,
Xenbase
Zhang,
The topological structure of connexin 26 and its distribution compared to connexin 32 in hepatic gap junctions.
1994,
Pubmed
